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Anti-cancer properties of glucosamine-hydrochloride in YD-8 human oral cancer cells: Induction of the caspase-dependent apoptosis and down-regulation of HIF-1α

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Author(s)
Chang-Wook JungJeong-Rang JoSang-Han LeeYu-Kyoung ParkNak-Kyun JungDae-Kyu SongJaeHoon BaeKi-Young NamJung-Sook HaIn-Sook ParkGy-Young ParkByeong-Churl JangJong-Wook Park
Keimyung Author(s)
Nam, Ki YoungPark, Jong WookSong, Dae KyuBae, Jae HoonJang, Byeong ChurlHa, Jung Sook
Department
Dept. of Dentistry (치과학)
Dept. of Physiology (생리학)
Dept. of Immunology (면역학)
Dept. of Molecular Medicine (분자의학)
Dept. of Laboratory Medicine (진단검사의학)
Journal Title
Toxicol In Vitro
Issued Date
2012
Volume
26
Issue
1
Keyword
YD-8 cellsGlucosamine-HClCaspasesER stressHIF-1aMcl-1
Abstract
Evidence suggests anti-tumor activities of glucosamine-hydrochloride (GS-HCl). In the present study, we
investigated anti-proliferative, growth suppressive and/or pro-apoptotic effects of GS-HCl on YD-8
human oral squamous cell carcinoma (OSCC) cells. Fundamentally, treatment with GS-HCl strongly inhib-
ited proliferation and induced apoptosis in YD-8 cells, as determined by MTS and DNA fragmentation
analyses. Of further note, as measured by Western analyses, GS-HCl treatment led to activation of cas-
pase-3, cytosolic accumulation of cytochrome c, down-regulation of Mcl-1 and HIF-1a, up-regulation
of GRP78, an indicator of ER stress, and generation of ROS in YD-8 cells. Importantly, results of pharma-
cological inhibition studies showed that treatment with z-VAD-fmk, a pan-caspase inhibitor, but not with
vitamin E, an anti-oxidant strongly blocked the GS-HCl-induced apoptosis in YD-8 cells. Analyses of addi-
tional cell culture works further revealed that GS-HCl had a strong growth suppressive effect on not only
YD-8 but also YD-10B and YD-38, two other human OSCC cell lines. These findings collectively demon-
strate that GS-HCl has anti-proliferative, anti-survival, and pro-apoptotic effects on YD-8 cells and the
effects appear to be mediated via mechanisms associated with the mitochondrial-dependent activation
of caspases, down-regulation of Mcl-1, and induction of ER stress. Considering HIF-1a as a tumor angio-
genic transcription factor, the ability of GS-HCl to down-regulate HIF-1a in YD-8 cells may further sup-
port its anti-cancer property. It is thus suggested that GS-HCl may be used as a potential anti-cancer drug
against human OSCC. Keywords:
YD-8 cells
Glucosamine-HCl
Caspases
ER stress
HIF-1a
Mcl-1
Keimyung Author(s)(Kor)
남기영
박종욱
송대규
배재훈
장병철
하정숙
Publisher
School of Medicine
Citation
Chang-Wook Jung et al. (2012). Anti-cancer properties of glucosamine-hydrochloride in YD-8 human oral cancer cells: Induction of the caspase-dependent apoptosis and down-regulation of HIF-1α. Toxicol In Vitro, 26(1), 42–50. doi: 10.1016/j.tiv.2011.10.005
Type
Article
ISSN
0887-2333
Source
https://www.sciencedirect.com/science/article/pii/S0887233311002712?via%3Dihub
DOI
10.1016/j.tiv.2011.10.005
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34655
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Dentistry (치과학)
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. School of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학)
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
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